Cesium carbonate → (R)-tert-Butyl 3-((2-chloropyrimidin-4-yl)oxy)pyrrolidine-1-carboxylate

HRID 1028127Notes

Reaction equation

HRID 1028127 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[OH:9][C@@H:10]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([O:9][C@@H:10]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 775312,4-DichloropyrimidineHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 60137519(R)-tert-Butyl 3-((2-chloropyrimidin-4-yl)oxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

2,4-Dichloropyrimidine (3.95 g, 26.5 mmol), tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (4.14 g, 22.11 mmol), and cesium carbonate (18 g, 55.3 mmol) were taken up in DMSO (44 ml). The reaction mixture was heated to 140° C. for 40 min, cooled to room temperature, and diluted with ethyl acetate. The mixture was washed with water (×2) and brine. The combined organics were dried over sodium sulfate, concentrated, and purified by Combiflash (ethyl acetate/hexanes) to afford tert-butyl (3R)-3-[(2-chloropyrimidin-4-yl)oxy]pyrrolidine-1-carboxylate.

Workup

  1. temperaturecooled to room temperature
  2. washThe mixture was washed with water (×2) and brine
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by Combiflash (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f0799b364ee147f38f69d212e6985721
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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